RNA interference (RNAi) is an RNA-guided gene silencing process within living cells that controls the expression of the targeted genes (Hannon 2002; Denli and Hannon 2003; Sontheimer 2005). There are two major types of small RNA molecules that are central to RNA interference, microRNAs (miRNAs) and small interfering RNAs (siRNAs).
MicroRNAs (miRNAs) are involved in a variety of human diseases by simultaneously suppressing many gene targets. Thus, the therapeutic value of miRNAs has been intensely studied. However, there are potential limitations with miRNA-based therapeutics such as relatively moderate impact on gene target regulation and cellular phenotypic control. Further, there are only a limited number of natural miRNAs to be used in RNAi. In contrast, siRNAs may result in efficient knockdown of a target gene, but may only target one gene at a time. Thus, there is a need in the art for miRNA-based therapeutics that are rationally designed to improve the efficiency of knockdown and are multi-functional to simultaneously target multiple genes.